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Current Molecular Pharmacology

Shahinda S R Alsayed, Chau Chun Beh, Neil R Foster, Alan D Payne, Yu Yu, Hendra Gunosewoyo
Mycolic acids (MAs) are the characteristic, integral building blocks for the mycomembrane belonging to the insidious bacterial pathogen Mycobacterium tuberculosis (M.tb). These C60-C90 long α-alkyl-β-hydroxylated fatty acids provide protection to the tubercule bacilli against the outside threats, thus allowing its survival, virulence and resistance to the current antibacterial agents. In the post-genomic era, progress has been made towards understanding the crucial enzymatic machineries involved in the biosynthesis of MAs in M...
October 25, 2018: Current Molecular Pharmacology
Alexander V Zholos, Olesia F Moroz, Maksim V Storozhuk
BACKGROUND: Millions of people worldwide are suffering from Alzheimer's disease (AD), and there are only symptomatic treatments available for this disease. Thus, there is a great need to identify drugs capable of arresting or reversing AD. Constituents of the spice turmeric, in particular curcuminoids, seem to be very promising, as evident from in vitro experiments and tests using animal models of AD. However, most of the clinical trials did not reveal any beneficial effects of curcuminoids in the treatment of AD...
October 12, 2018: Current Molecular Pharmacology
Ricardo Jorge Dinis-Oliveira, Carolina Lanca Pereira, Diana Dias da Silva
BACKGROUND: Mescaline (3,4,5-trimethoxyphenethylamine), mainly found in the Peyote cactus (Lophophora williamsii), is one of the oldest known hallucinogenic agents that influence human and animal behavior, but its psychoactive mechanisms remain poorly understood. OBJECTIVES: This article aims to fully review pharmacokinetics and pharmacodynamics of mescaline, focusing on the in vivo and in vitro metabolic profile of the drug and its implications for the variability of response...
October 10, 2018: Current Molecular Pharmacology
Keywan Mortezaee, Nasser Hashemi Goradel, Peyman Amini, Dheyauldeen Shabeeb, Ahmed Eleojo Musa, Masoud Najafi, Bagher Farhood
BACKGROUND: Radiotherapy is a treatment modality for cancer. For better therapeutic efficiency, it could be used in combination with surgery, chemotherapy or immunotherapy. In addition to its beneficial therapeutic effects, exposure to radiation leads to several toxic effects on normal tissues. Also, it may induce some changes in genomic expression of tumor cells, thereby increasing the resistance of tumor cells. These changes lead to the appearance of some acute reactions in irradiated organs, increased risk of carcinogenesis, and reduction in the therapeutic effect of radiotherapy...
October 10, 2018: Current Molecular Pharmacology
Faith A A Kwa, Merrole F Cole-Sinclair, Miroslav K Kapuscinski
BACKGROUND: Treatment of haematological malignancies with conventional DNA-damaging drugs, such as chlorambucil (CLB), commonly results in p53-dependent chemo-resistance. Chromatin modifying agents, such as histone deacetylase inhibitors (HDACIs), sodium butyrate (NaBu) and trichostatin A (TSA), may reverse chemo-resistance by modulating the activity of chromatin remodeling enzymes and/or genes that control cell proliferation, differentiation and survival. OBJECTIVE: This study examined the potential use of HDACIs and CLB combination therapies in an in vitro chemo-resistant leukaemia model...
October 10, 2018: Current Molecular Pharmacology
Maryam Naserian, Elham Ramazani, Mehrdad Iranshahi, Zahra Tayarani-Najaran
BACKGROUND: Besides the first-line medication for the treatment of type 2 diabetes, the growth inhibitory activity of metformin alone or in combination of conventional chemotherapeutics has been addressed on a panel of cell lines. In this study, we investigated the cytotoxicity and apoptosis of the metformin alone and in combination with dacarbazine in Raji and Ramos lymphoma cell lines. METHODS: Cell viability and apoptosis measured using resazurin assay, flow cytometry of PI stained cells and western blot analysis...
August 30, 2018: Current Molecular Pharmacology
Seyede Hadis Momeni Hasan Abadi, Alireza Shirazi, Ali Mohammad Alizadeh, Vahid Changizi, Masoud Najafi, Solmaz Khalighfard
PURPOSE: Radiation causes damage to irradiated tissues and also tissues that do not receive direct irradiation through a phenomenon called bystander effects. Melatonin as a potent antioxidant and anti-inflammatory agent is known for protection of normal tissues against ionizing irradiation. In addition, some studies have suggested that Melatonin may have some anti-cancer properties. Although the complete mechanisms remain unknown, it can act via immunomodulatory effects. The aim of this study was to evaluate the effect of pretreatment with melatonin on oxidative damage caused by direct irradiation and bystander effects on the lung and heart tissue after xenograft mice colon cancer irradiation in Balb/c mice...
August 30, 2018: Current Molecular Pharmacology
Peyman Amini, Hanifeh Mirtavoos-Mahyari, Elahe Motevaseli, Dheyauldeen Shabeeb, Ahmed Eleojo Musa, Mohsen Cheki, Bagher Farhood, Rasoul Yahyapour, Alireza Shirazi, Nouraddin Abdi Goushbolagh, Masoud Najafi
BACKGROUND: Melatonin is a natural body product that has shown potent antioxidant property against various toxic agents. For more than two decades, the abilities of melatonin as a potent radioprotector against toxic effects of ionizing radiation (IR) has been proved. However, in recent years, several studies have been conducted to illustrate how melatonin protects normal cells against IR. Studies proposed that melatonin is able to directly neutralize free radicals produced by IR, leading to the production of some low toxic products...
August 2, 2018: Current Molecular Pharmacology
Ana Carolina Antunes Naime, Jessica Oliveira Frade Ganaes, Maria Elisa Lopes-Pires
OBJECTIVE: Sepsis, a serious and life threatening complication arising from infection caused by lipopolysaccharide, is a complex inflammatory syndrome, and one of the main causes of death in intensive care units (ICU). It is characterized as an over-response of pro-coagulant agents promotes coagulopathy and thrombus formation, resulting in disseminated intravascular coagulation (DIC). Furthermore, it can cause multiple organ dysfunction and hypotension (septic shock) resulting in death...
June 19, 2018: Current Molecular Pharmacology
Rasoul Yahyapour, Dheyauldeen Shabeeb, Mohsen Cheki, Ahmed Eleojo Musa, Bagher Farhood, Abolhasan Rezaeyan, Peyman Amini, Hengameh Fallah, Masoud Najafi
BACKGROUND: Nowadays, ionizing radiations are used for various medical and terroristic aims. These purposes involve exposure to ionizing radiations. Hence, people are at risk for acute or late effects. Annually, millions of cancer patients undergo radiotherapy during their course of treatment. Also, some radiological or nuclear events in recent years pose a threat to people, hence the need for radiation mitigation strategies. Amifostine, the first FDA approved radioprotector, has shown some toxicities that limit its usage and efficiency...
June 19, 2018: Current Molecular Pharmacology
Rhiannon E Roberts, Geetha L Elumalai, Maurice B Hallett
BACKGROUND AND OBJECTIVE: Ezrin links the cortical cytoskeleton to the plasma membrane and plays a role in regulating cell shape change. Recently NSC668394 has been shown to inhibit a key step for its activity, i.e. phosphorylation at threonine 567. In neutrophils, another key regulatory step is the Ca2+-mediated cleavage of ezrin by calpain. METHODS: In this paper we use NSC668394 as a pharmacological inhibitor to investigate the interplay between these two steps in regulating neutrophil shape change...
May 15, 2018: Current Molecular Pharmacology
Keiji Tabuchi, Akira Hara
BACKGROUND AND OBJECTIVE: Sphingolipid metabolites, including ceramide, sphingosine, and their phosphorylates (ceramide-1-phosphonate [C1P] and sphingosine-1-phosphate [S1P]), regulate diverse cellular processes including apoptosis, the cell cycle, and cellular differentiation. Recent studies have shown that these sphingolipid metabolites are generated in response to ototoxic agents and play important roles in determining the fate of cochlear hair cells in ototoxic injury. METHODS: This review summarizes the current knowledge on the roles of sphingolipid mediators in cochlear ototoxicity...
May 15, 2018: Current Molecular Pharmacology
Jagdish Kumar Sahu, Arun Kumar Mishra
BACKGROUND: The brain is a vital part of the central nervous system (CNS), characterized by the presence of soft tissue in its internal structure which protects itself. Research on design of drugs for CNS disorders is in progress and up to date information is required for further investigation. OBJECTIVE: The present paper is written with the objective to compile all the available data and information on CNS disorders and CNS acting drugs. CNS acting drugs are important to consider because some drugs get ineffective owing to incapability to efficiently deliver and sustain them within the brain for effective treatment...
2018: Current Molecular Pharmacology
Suhang Hua, Xiangyu Kong, Binbin Chen, Wenxin Zhuang, Qian Sun, Wei Yang, Wenzhi Liu, Yongxing Zhang
OBJECTIVE: To explore the mechanism by which lobaplatin, as monotherapy and in combination with paclitaxel, inhibits the proliferation of human gastric cancer SGC-7901 cells. METHODS: After treatment, the MTT assay was used to assess cell viability; cell cycle distribution was evaluated flow-cytometrically. Western blot was used to quantitate cyclin D1, E1, B1, and Cdk2/4 protein levels. RESULTS: Lobaplatin and paclitaxel inhibited SGC-7901 cell growth in a concentration and timedependent manner, with IC25 values at 48h of 1...
2018: Current Molecular Pharmacology
Andy Awad, Pamela El Khoury, Brigitte Wex, Roy A Khalaf
BACKGROUND: Candida albicans is present as part of the normal gut flora and detected in the oral cavities and GI tracts of around fifty percent of adults. Benign colonization can turn pathogenic causing a variety of mild to severe infections. In a pathogen, the cell wall and cell surface proteins are major antigenic determinants and drug targets as they are the primary structures that contact the host. Cell surface proteins perform a variety of functions necessary for virulence such as adhesion, host degradation, resistance to oxidative stress, and drug resistance...
2018: Current Molecular Pharmacology
Michaila Michalatou, Maria Eleni Androutsou, Markos Antonopoulos, Demetrios V Vlahakos, George Agelis, Anthony Zulli, Tawar Qaradakhi, Kathleen Mikkelsen, Vasso Apostolopoulos, John Matsoukas
BACKGROUND: The Renin Angiotensin System (RAS) is pharmacologically targeted to reduce blood pressure, and patient compliance to oral medications is a clinical issue. The mechanisms of action of angiotensin receptor blockers (ARBs) in reducing blood pressure are not well understood and are purported to be via a reduction of angiotensin II signaling. OBJECTIVE: We aimed to develop a transdermal delivery method for ARBs (losartan potassium and valsartan) and to determine if ARBs reveal a vasodilatory effect of the novel RAS peptide, alamandine...
2018: Current Molecular Pharmacology
Shivani Verma, Saurabh Sharma
BACKGROUND: Tyrosine-protein phosphatase is an enzyme that functions in a unit with tyrosine kinases to regulate signaling pathways. Several members of the PTP family link to human disease predisposition such as PTP1B, SH2, DEP1, and inhibition of these enzymes may represent an effective palliative therapy. OBJECTIVE: This review aims to summarize the rapidly developing role of the PTPs in various physiological and pathological states. RESULTS: Pharmacological inhibition of protein tyrosine phosphatase has been found to reduce endothelial dysfunction in different cardiovascular diseases related to metabolic disorders and it can be helpful for the management of other brain disorders associated with perhaps even in normal, agerelated cognitive decline...
2018: Current Molecular Pharmacology
Mohsen Cheki, Rasoul Yahyapour, Bagher Farhood, Abolhassan Rezaeyan, Dheyauldeen Shabeeb, Peyman Amini, Saeed Rezapoor, Masoud Najafi
BACKGROUND: Each year, millions of people die from cancer. Radiotherapy is one of the main treatment strategies for cancer patients. Despite the beneficial roles of treatment with radiation, several side effects may threaten normal tissues of patients in the years after treatment. DISCUSSION: Moreover, high incidences of second primary cancers may reduce therapeutic ratio of radiotherapy. The search for appropriate targets of radiosensitization of tumor cells as well as radioprotection of normal tissues is one of the most interesting aims in radiobiology...
2018: Current Molecular Pharmacology
Nabeela K Dulull, Daniel A Dias, Thilini R Thrimawithana, Faith A A Kwa
BACKGROUND: In age-related macular degeneration, oxidative damage and abnormal neovascularization in the retina are caused by the upregulation of vascular endothelium growth factor and reduced expression of Glutathione-S-transferase genes. Current treatments are only palliative. Compounds from cruciferous vegetables (e.g. L-Sulforaphane) have been found to restore normal gene expression levels in diseases including cancer via the activity of histone deacetylases and DNA methyltransferases, thus retarding disease progression...
2018: Current Molecular Pharmacology
George Liapakis
No abstract text is available yet for this article.
2018: Current Molecular Pharmacology
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